Utility of tumor marker levels in predicting survival of patients with appendiceal adenocarcinoma.
Authors: Abdelrahman M.G. Yousef, Aditya More, Mohammad A. Zeineddine, Saikat Chowdhury, Yue Gu, Julia Dansby, Zahra Alavi Naini, Abhineet Uppal, Kanwal Pratap Singh Raghav, Michael J. Overman, Keith F. Fournier, John Paul Y.C. Shen
Journal: Journal of Clinical Oncology (2023)

221 Background: Due to the rarity of appendiceal adenocarcinomas (AA), systematic study of these tumors has been limited. Thus, guidelines for the diagnosis and treatment of AA are often based on other related tumor types such as colorectal cancer. However, given that AA has been shown to be molecularly and functionally distinct, there is a need for focused clinical data to guide disease management. In AA, tumor marker levels are used by some practitioners to monitor response to treatment and aid in diagnosis. This study evaluates the association of elevated tumor marker levels with survival outcomes. Methods: The MDACC database was queried to identify patients with AA between 1997 to 2022. Patients with reported values for the tumor markers CA-125 (n=1076), CA 19-9 (n=1060), and CEA (n=1249) were then selected for analysis. Elevation of tumor markers was defined as above the laboratory upper limit of normal (CA-125 &gt; 37 U/mL, CA 19-9 &gt; 37 U/mL, and CEA &gt; 3 ng/mL and survival outcomes were compared with a log-rank (Mantel-Cox) test. This analysis was repeated while controlling for tumor grade, which was defined by low-grade: well, well to moderately differentiated and high-grade: moderate, moderate to poor, and poorly differentiated. Results: Elevated CA-125 was predictive of overall survival in all patients with median survival not-yet-reached for those with normal CA-125 vs. 87.4 months for those with elevated CA-125 (HR: 5.8, p &lt; 0.0001). Similarly, elevated CA 19-9 and CEA were also predictive of overall survival (HR: 2.8, 4.6, respectively, p &lt; 0.0001 for each). Given that tumor grade is the primary driver of prognosis in AA, survival analysis was repeated while controlling for tumor grade. While elevated levels of all tumor markers were predictive of overall survival for both low-grade and high-grade tumors, elevated CA-125 was an especially strong predictor of survival in patients with high-grade tumors (OS: 69.8 months vs. not-yet-reached, HR: 14.3, p &lt; 0.0001). Moreover, high-grade patients with elevated CA-125 had a reduced 5-year survival rate of 56% vs. 91%. Elevated CA-125 also stratified 5-year survival rate in low-grade patients (83% vs. 99%). Elevated levels of CA 19-9 and CEA were strongly predictive of overall survival for patients with low-grade tumors (HR: 10.6, 26.8, respectively, p &lt; 0.0001 for each). Notably, patients with low-grade tumors expressing normal levels of CA 19-9 or CEA had excellent 5-year survival rates of 99% and 100%, respectively. Conclusions: These results highlight the utility of using tumor marker levels in conjunction with tumor grade to more accurately predict prognosis in AA. CA 19-9 and CEA were particularly useful indicators of outcome in patients with low-grade AA, while CA-125 had greatest prognostic value in high-grade tumors.